Trial Title:
BMX-001 + Paclitaxel in Adult Patients With Advanced, Recurrent, Metastatic Ovarian or Endometrial Cancer
NCT ID:
NCT06620029
Condition:
Ovarian Neoplasms
Endometrial Cancer, Endometrial Neoplasm
Conditions: Official terms:
Neoplasms
Endometrial Neoplasms
Ovarian Neoplasms
Paclitaxel
Conditions: Keywords:
BMX-001 plus Paclitaxel
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
Dose finding stage followed by an expansion cohort.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BMX-001
Description:
BMX-001 consists of a porphyrin ring with pyridyl groups attached at each of the four
methane bridge carbons. The nitrogen in the pyridyl ring is at the 2 position and has a
side chain consisting of six carbons with an ether linkage. A manganese atom is chelated
into the porphyrin ring and is the active center of the molecule. This molecule is an
enzymatic scavenger of free radical species operating at close to diffusion-limited
rates. BMX-001 (7-28 mg) will be given by subcutaneous (s.c.) injection starting on Day
1, Day 8, Day 15, and Day 22 of each 28-day PTX treatment cycle.
Arm group label:
BMX-001 + PTX
Intervention type:
Drug
Intervention name:
Paclitaxel (Taxol)
Description:
Paclitaxel will be given via IV infusion at a dose = 80 mg/m2 on Day 1, Day 8, Day 15,
and Day 22 of each 28-day treatment cycle and will be sourced from standard commercial
sources. Appropriate pretreatment prior to PTX will be given as per institutional
standards. PTX management for any adverse event (AE) in any cycle, reasonably attributed
to the chemotherapy agent that requires dose interruption should be managed per package
insert, and/or institutional guidelines. Dose modification recommendations are provided
in protocol to provide general consistency with dosing. Study Treatment dosing BMX-001
should continue even if the PTX is omitted. The subject may continue on PTX if the AE
does not prohibit dosing per institutional practice. Grade 3 or higher infusion PTX
reactions or recurrent infusion reactions may require permanent discontinuation of PTX.
PTX may be continued in select patients using institutional desensitization protocol.
Arm group label:
BMX-001 + PTX
Summary:
This research project addresses the urgent need for novel therapeutic strategies to
overcome chemotherapy resistance and mitigate chemotherapy-induced peripheral neuropathy
(CIPN) in patients with recurrent ovarian and endometrial cancers, which are among the
most lethal gynecologic malignancies worldwide. The study focuses on BMX-001, a
redox-active manganese metalloporphyrin compound that uniquely combines the ability to
enhance anti-tumor efficacy and protect normal tissues from the toxic effects of
chemotherapy, specifically paclitaxel (PTX). PTX, despite being a cornerstone of
treatment, is associated with significant dose-limiting neurotoxicity, which severely
impacts patients quality of life and limits the use of subsequent therapies. BMX-001 has
demonstrated potential in preclinical models to not only augment the anti-tumor effects
of PTX but also reduce PTX-induced neuropathy.
The research will be conducted through a single-site, Phase 1/2 clinical trial led by the
Duke Cancer Institute. The trial aims to determine the recommended Phase 2 dose of
BMX-001 when combined with weekly PTX and to evaluate the clinical activity of this
combination therapy. Specifically, the trial will assess the safety, tolerability, and
potential to double the dose of BMX-001, which is hypothesized to further enhance the
efficacy of PTX without increasing toxicity. The study's specific aims include
establishing the recommended dose for expansion, assessing objective response rates
(ORR), and quantifying the reduction in PTX-induced neurotoxicity using validated
questionnaires and monofilament testing. The project also incorporates the analysis of
circulating tumor DNA (ctDNA) as a biomarker for treatment response, adding a layer of
precision to the evaluation of the therapy response impact on tumor burden.
The outcomes of this research have the potential to significantly improve treatment
protocols for patients with chemo-resistant gynecologic cancers by offering a therapy
that enhances tumor control while protecting against debilitating side effects.
Successful completion of this trial will lay the groundwork for larger, definitive trials
and may extend the benefits of BMX-001 to other solid tumors, ultimately contributing to
better survival outcomes and quality of life for a broader patient population.
Detailed description:
This clinical trial is a proof-of-concept Phase 1/2 study aimed at establishing the
recommended Phase 2 dose (RP2D) of BMX-001 when administered in combination with weekly
paclitaxel (PTX) in patients with advanced, metastatic ovarian or endometrial cancer. The
rationale for this open-label trial is twofold: (1) response rates to weekly PTX in
patients with platinum-resistant ovarian cancer (PROC) are generally low, and when a
response is achieved, its duration is often short, necessitating novel therapeutic
approaches to improve outcomes; (2) weekly PTX is associated with dose-limiting side
effects, particularly chemotherapy-induced peripheral neuropathy (CIPN), which
significantly impacts patients quality of life.
The trial includes a dose-finding stage designed to assess the safety and dose-limiting
toxicities (DLTs) of the combination treatment. The study will use a Bayesian Optimal
Interval (BOIN) design to test the safety of weekly BMX-001 injections in combination
with weekly PTX. The goal is to determine if BMX-001 can be safely administered at
increasing doses while enhancing both the efficacy of treatment as well as diminishing
chemotherapy side effects in patients with recurrent, advanced ovarian and endometrial
cancers.
Patients in the dose-escalation phase will receive up to 16 doses over an 8-week period.
All participants will receive PTX at a dose of 80 mg/m² on the first day of each weekly
cycle. The starting dose of BMX-001 will be 28 mg subcutaneously on the first day of each
weekly cycle. Cohorts of three patients will be treated and evaluated for DLTs
sequentially. If the starting dose is well-tolerated, subsequent cohorts will escalate to
higher doses, with a maximum of 28 mg followed by 28 mg BMX-001 given 4-6 hours apart on
the same day each week. Should any patients at Dose Level 1 experience DLTs, the dose
will be de-escalated according to the BOIN design to Dose Level -1 (14 mg/week), and if
necessary, further to Dose Level -2 (7 mg/week), which is the final de-escalation dose
group.
Upon completion of the dose-finding phase, an expansion cohort will be enrolled at the
RP2D. The study will enroll up to 27 patients in this trial. The primary outcome measure
is to establish the RP2D of BMX-001 in combination with PTX. Secondary outcomes include
evaluation of preliminary efficacy based on objective response rate (ORR) using RECIST v
1.1 per investigator assessment endpoints and obtaining a description of patient-reported
outcomes of health related quality of life (HRQoL) quality of life (QoL) using
FACT/GOG-NTX Questionnaire and monofilament testing.
Other outcome measures to be assessed in all patients include characterization of the
pharmacokinetic profile of BMX-001 when delivered in combination with PTX in recurrent
ovarian or endometrial cancer and also to assess correlations between B cell
lymphoma/leukemia 2 (BCL2), Nrf2, TNF-alpha, and NFkB RNA and protein expression and
activation, ctDNA, and clinical responses. This initial single arm trial is limited to 27
subjects based on the funds available in this SBIR. In spite of the small sample size,
the study expects to obtain sufficient data to enable design a subsequent randomized
trial that would meet registration requirements
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Recurrent advanced metastatic ovarian or endometrial cancer that progressed during
or following prior SOC therapy
2. Aged 18 years or older
3. Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 to 1
4. Ability to understand and willingness to give written informed consent
5. Measurable disease according to RECIST v1.1 or assessable disease based on presence
of malignancy pleural effusion or ascites, or disease that does not meet measurable
criteria.
6. Negative serum pregnancy test within 48 hours of dosing if indicated.
7. Adequate bone marrow function
8. Adequate hepatic function
9. Adequate renal function as determined by calculated or measured creatinine clearance
≥30 mL/min (using Cockcroft- Gault equation) or serum creatinine < 1.5 X
institutional ULN
10. Full recovery from all recent surgery on start date of treatment; at least 1 week
must have elapsed from the time of a minor surgery (port placement at any time is
acceptable); from the date of treatment at least 21 days must have elapsed from the
time of a major surgery. Must have fully recovered from all surgery-related
toxicities to Grade 1 or less
11. At least 28 days between termination of prior anticancer or hormonal therapy and
first administration of BMX-001
Exclusion Criteria:
1. Residual Grade 2 peripheral neuropathy
2. Untreated central nervous system (CNS) metastases (surgery and/or radiotherapy),
Subjects requiring corticosteroid therapy for the management of CNS metastases may
not be on >10 mg/day prednisone or equivalent. Subjects that have demonstrated
signs or symptoms of neurologic instability for 28 days or less prior to enrollment.
3. Is being treated with concurrent anticancer therapy or other interventional
treatments administered for their underlying cancer
4. Subjects who have received prior therapy with weekly PTX in the recurrent setting.
5. Clinically significant cardiac disease.
6. History of or present CNS disease unrelated to cancer, unless adequately treated
with standard medical therapy (eg, uncontrolled seizures)
7. Nonhealing wound, ulcer, or bone fracture
8. Serious active infection requiring IV antibiotics and/or hospitalization within 7
days of enrollment
9. Known severe hypersensitivity to any of the study drugs or excipients, including
history of allergic, anaphylactic, or other severe hypersensitivity reactions to
fusion proteins, products containing Cremophor EL (eg, cyclosporin for injection
concentrate and teniposide for injection concentrate)
10. Require regular blood transfusions, platelet transfusions, or granulocyte colony
stimulating factor.
11. For female patients of childbearing potential, the following are exclusion criteria,
as applicable:
12. Refusal to use highly effective method of contraception or to practice true
abstinence during treatment and for 6 months after the last dose of study drug
13. Pregnant or breast feeding;
14. Presence of any other condition that may increase the risk associated with
enrollment on the study, interfere with data interpretation, or make the patient
inappropriate for study enrollment in the opinion of the treating investigator
15. Prior treatment with or participation in a study with BMX-001
16. A history of additional risk factors for Torsades de Pointes (e.g., congestive heart
failure, hypokalemia, known family history of Long QT Syndrome).
17. Severe, active co-morbidity, as defined in protocol.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Duke Cancer Institute
Address:
City:
Durham
Zip:
27710
Country:
United States
Contact:
Last name:
Angeles Secord, MD
Phone:
919-684-3765
Email:
angeles.secord@duke.edu
Investigator:
Last name:
Angeles Secord, MD
Email:
Principal Investigator
Start date:
April 1, 2025
Completion date:
July 31, 2027
Lead sponsor:
Agency:
BioMimetix JV, LLC
Agency class:
Industry
Source:
BioMimetix JV, LLC
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06620029
